Stereoselective synthesis of (R)-1-chloro-3(3,4-difluorophenoxy)-2-propanol using lipases from Pseudomonas aeruginosa in ionic liquid-containing system

Abstract Direct transesterification of ( R , S )-1-chloro-3-(3,4-difluorophenoxy)-2-propanol ( rac -CDPP) (a key intermediate in the synthesis of the chiral drug ( S )-lubeluzole) with vinyl butyrate by lipases from Pseudomonas aeruginosa ( P. aeruginosa ) MTCC 5113 was performed in hexane with ionic liquids (ILs) 1-butyl-3-methyl imidazolium hexafluorophosphate [BMIm][PF 6 ] and 1-butyl-3-methyl imidazolium tetrafluoroborate [BMIm][BF 4 ] as co-solvents. The maximum conversion (>49%) and enantiomeric excess (ee > 99.9%) was achieved in 6 h of incubation at 30 °C with [BMIm][PF 6 ] as co-solvent in a two-phase system. The enzyme was able to perform with the same specificity even at 60 °C in the presence of ILs. It was possible to use lipases repeatedly for more than 10 times while still maintaining absolute enantioselectivity and reactivity. Stability studies on lipases from P. aeruginosa in ILs revealed the fact that the enzyme constancy and the reactivity in catalyzing transesterification of rac -CDPP into ( S )-1-chloro-3-(3,4-difluorophenoxy)-2-butanoate was of the order of [BMIm][PF 6 ] > [BMIm][BF 4 ] in two-phase system.

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